Flat administration forms to be applied in the oral region and on mucous membranes of the mouth are known. U.S. Pat. No. 3,444,858 describes medicament strips based on a gelatin-like material. Also, pharmaceutical products in the form of a film have already been described in the early 70 s. DE-A 24 49 865 described medicinal active substance carriers in the form of a film, containing different active substances and active substance concentrations.
U.S. Pat. No. 4,128,445 discloses technical solutions in loading of carrier material with active substances and, in this context, goes into the subsequent addition of active substance preparations by applying them onto pre-fabricated film-shaped preparations. The document describes loading methods in dry and moist form aiming at achieving a uniform, subsequent distribution of active substance on a layer.
Canadian patent application No. 492 040 describes a process for manufacture of film-shaped preparations employing active substance along with gelatin, agar, gluten, carboxyvinyl polymer, polyhydric alcohol, vegetable mucilage, wax or water.
Also known are proposals for application of active substance-loaded films or foils outside the pharmaceutical field. Thus, in EP-A 219 762 a water-soluble film of starch, gelatin, glycerol or sorbite is disclosed, which is coated using the roll coating method. In this connection, it is stated that such dosing forms may also be produced employing ingredients of chemical reagents, aromatics and the like.
DE-A 36 30 603 provides for a flat dosage form, on a carrier material (release film), to be peelable in doses.
Drug containing film-shaped systems and their advantages are further known from U.S. Pat. No. 5,047,244. These systems comprise a double-layered structure of a water swellable layer and a non-water-swellable barrier film. The use of polymers such as polyethylene glycol, the use of colloidal silicon dioxide, of bioadhesive (e.g. carboxy-functional) polymers, but also of polyvinyl alcohol, and of a number of other auxiliary substances is likewise known from the above publication.
A preparation suitable for making film-shaped aromatics-containing preparations is described by EP-A 460 588. A composition comprising 20 to 60 weight-% of film former, 2 to 40 weight-% of gel former, 0.1 to 35 weight-% of active substance or aromatic, and a maximum of 40 weight-% of an inert filling agent is regarded as affording particular advantages. As a gel former, polyvinyl alcohol is mentioned besides other ingredients. However, as it turns out, the gel-forming properties of polyvinyl alcohol are only partially compatible with the film formers mentioned in this written document. A portion of 20 weight-%, and more, of film-former—mostly a sugar derivative, polyethylene glycol, etc.—lead to considerable loss of aroma occurring already in thin layer drying, which is part of the production process.
The films or coatings to which the instant invention is related are based on organic raw materials or on a mix of such substances. These are preferably water-soluble substances. Such organic raw materials include polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, cellulose derivatives, polyvinyl acetate, polyetlylene glycol, alginate, carrageenan, xanthan, gelatine and other water-soluble polymers known to the skilled artisan, as well as mixtures and copolymers of such substances. If desired, such films or coatings may also include fillers such as mannitol, lactose, calcium phosphate, glucose, sorbitol etc., active substances such as drugs, aroma substances, menthol etc., sweeteners such as cyclamate, flavours such as glutamate, and other ingredients, including in some cases volatile ingredients. These films may also have mucoadhesive properties.
Usually, the films and coatings are produced by means of casting methods or reverse coating methods. The manufacture of thin films or coatings is accomplished according to the present invention in that initially a coating mass is prepared containing organic substances which are suitable for forming a film, or a coating, for instance, polymers such as polyvinyl alcohol, polyvinyl pyrrolidone, cellulose derivatives, polyvinyl acetate, polyetlylene glycol, alginate, carrageenan, xanthan, gelatine and other water-soluble polymers known to the skilled artisan, as well as mixtures or copolymers of such substances. Preferably, these substances are completely or partially dissolved or dispersed in water. Apart from water, other solvents may be used as well, e.g. alcohols such as methanol, ethanol, propanol or solvent mixtures such as water-alcohol mix.
The coating composition may further comprise various additives, e.g. fillers such as mannitol, lactose, calcium phosphate, glucose, sorbitol etc., and/or active substances such as drugs, aroma substances, menthol etc., and/or sweeteners such as cyclamate, flavours such as glutamate, and other ingredients, including in some cases volatile ingredients.
The coating mass thus obtained is subsequently applied to a web-shaped support material, using the casting method or reverse coating method. As support material, a web or sheet of paper, plastic, metal or a composite of two or more of these materials may be used.
The product web may, for example, have a width of about 0.1 m to about 2 m. Preference is given a width in the range of from 0.5 to 1.6 m. The films or coatings applied to the support layer are preferably thin, that means, their thickness ranges of from about 10 to 500 μm, preferably from 50 to 200 μm.
The coated support material, i.e. the composite of support and coating composition, is thereafter transferred into a drying device (drying oven) and transported through the same, preferably continuously.
The dried composite is then wound up and stored.
The above-described method, however, has the disadvantage that parts of the active-ingredient diffuse from the coating into the support material during the contact period. For that reason, used support material cannot be used again for the preparation of the same or other products in web form, since an unpredictable quantity of active-ingredient disappears from the coating or diffuses back from the support material into the coating during the contact period. Thus, big amounts of waste support material arise during the conventional process making the preparation expensive and environmentally less favourable.